A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19

OBJECTIVE: To assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: We did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death). RESULTS: The mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5–28) in the standard of care group (hazard ratio, 1.22; 95% CI, 0.70–2.15; p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56; 95% CI, 0.16–1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel. CONCLUSIONS: In this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04371978.